The present invention relates to a process for the production of L-threonine or L-isoleucine by fermentation. L-threonine and L-isoleucine are useful as a medicament such as an amino acid preparation and can also be used as an animal feed additive.
Several processes for producing L-threonine by fermentation comprising the use of a microorganism belonging to the genus Escherichia are known including a process using a microorganism having a borrelidin sensitivity (Japanese Published Examined Patent Application No. 6752/76), a process using a microorganism requiring diaminopimelic acid and methionine for growth and having a threonine biosynthetic system with resistance to feedback inhibition by threonine (Japanese Published Examined Patent Application No. 10037/81), and a process using microorganisms having a resistance to at least one of rifampicin, lysine, methionine, aspartic acid, and homoserine, or with the decreased ability to decompose L-threonine (Japanese Published Unexamined Patent Application No. 273487/88, U.S. Pat. No. 5017483).
The present applicant bas applied for a patent on a process that uses a microorganism having a resistance to L-serine and/or ethionine (Japanese Published Unexamined Patent Application No. 259088/91, European Publication No. 445830) and a process that uses a microorganism having a resistance to L-phenylalanine and/or L-leucine in the presence of L-lysine (Japanese Patent Application No. 224259/91). On the other hand, few reports have been made for a process for the production of L-isoleucine by fermentation comprising the use of a microorganism belonging to the genus Escherichia, or as a process using a mutant. Rather, only a process that uses a microorganism having a resistance to an isoleucine analogue and further having a resistance to arginine hydroxamate and/or ethionine has been applied for a patent by the present applicant (Japanese Patent Application No. 294420/91).
In addition, there is also known a process that uses a microorganism belonging to the genus Escherichia having the activity of threonine deaminase or acetohydroxy acid synthase (i.e., key enzymes of synthesizing L-isoleucine) increased by recombinant DNA technology (Japanese Published Unexamined Patent Application No. 458/90). This prior art process, however, is not insufficient since the yield of isoleucine formed is low.